fosA7: a silent fosfomycin resistance gene in Salmonella?
Authors: Jing Wang, Qiuchun Li, Yue Jiang, Zhenyu Wang, Xinan Jiao
Journal: The Lancet Microbe (2023)

The emergence and global dissemination of fosfomycin-resistant Gram-negative bacteria have become a serious global public health problem.1Ito R Mustapha MM Tomich AD et al.Widespread fosfomycin resistance in Gram-negative bacteria attributable to the chromosomal fosA gene.mBio. 2017; 8e00749–17Crossref PubMed Scopus (114) Google Scholar Daniel F M Monte and colleagues2Monte DFM Doi Y Lincopan N High prevalence and global distribution of fosfomycin resistance genes in Salmonella serovars.Lancet Microbe. 2023; (S2666-5247(23)00261-6)Summary Full Text Full Text PDF Google Scholar reported high prevalence (26 165 [4·75%] of 550 780) and global distribution of fosfomycin resistance genes—fosA7 and fosA3 in Salmonella serovars in a Correspondence published in The Lancet Microbe. Considering the One Health framework,3Ghai RR Wallace RM Kile JC et al.A generalizable one health framework for the control of zoonotic diseases.Sci Rep. 2022; 12: 8588Crossref PubMed Scopus (23) Google Scholar these findings about fosfomycin resistance in Salmonella are concerning.2Monte DFM Doi Y Lincopan N High prevalence and global distribution of fosfomycin resistance genes in Salmonella serovars.Lancet Microbe. 2023; (S2666-5247(23)00261-6)Summary Full Text Full Text PDF Google Scholar We conducted a retrospective study to screen whole-genome sequences (unpublished) of 729 Salmonella enterica isolates collected from different sources in China between 2019 and 2022, and found a high prevalence of fosfomycin resistance genes with 78 (10·70%) of 729 isolates harbouring fosA7 and 63 (8·64%) of 729 harbouring fosA3 (appendix pp 1–2). Among the recently identified fosA7 and its eight alleles (fosA7.2–fosA7.9), seven with 95·98–99·76% nucleotide sequence identity were specifically detected in Salmonella, resulting in one to seven amino acid substitutions (appendix pp 3–4). We detected fosA7.2 (Salmonella enterica serovar Agona), fosA7.3 (Salmonella enterica serovar Derby and Salmonella enterica serovar Idikan), fosA7.4 (Salmonella enterica serovar Meleagridis), and fosA7.6 (Salmonella enterica serovar Sandiego) in this study. Surprisingly, all fosA3-positive isolates were resistant to fosfomycin, whereas all fosA7-positive isolates were susceptible (appendix pp 1–2). Further analysis of the whole genomes of 78 fosA7-positive isolates (GenBank accession number PRJEB66432), combined with fosA7.7-positive or fosA7.8-positive Salmonella enterica serovar Reading and Salmonella enterica serovar Alachua strains in the National Center for Biotechnology Information database, revealed that all isolates carried the fosA7 gene within the chromosome. The genetic regions of five fosA7 alleles (except fosA7.2 and fosA7.8) identified in Salmonella were similar (97·83–98·35% identity, 95·56–98·75% coverage) to the corresponding region (∼24·3 kb) of the first detected fosA7 (appendix p 5) in Salmonella enterica serovar Heidelberg.4Rehman MA Yin X Persaud-Lachhman MG Diarra MS First detection of a fosfomycin resistance gene, fosA7, in Salmonella enterica serovar Heidelberg isolated from broiler chickens.Antimicrob Agents Chemother. 2017; 61: e00410-e00417Crossref PubMed Scopus (68) Google ScholarSee Online for appendices See Online for appendices The function of fosA7 and its alleles remains unclear, given the absence of a fosfomycin-resistant phenotype in our isolates. Thus, despite the high fosA7 prevalence observed in Salmonella strains worldwide,2Monte DFM Doi Y Lincopan N High prevalence and global distribution of fosfomycin resistance genes in Salmonella serovars.Lancet Microbe. 2023; (S2666-5247(23)00261-6)Summary Full Text Full Text PDF Google Scholar caution should be exercised when determining the clinical relevance of this fosfomycin resistance gene. These findings highlight the importance of antimicrobial susceptibility testing when whole-genome sequencing might not provide a definitive assessment. Although fosA7 might not currently present a great public health concern, the possibility of increased fosfomycin resistance development cannot be excluded if it is captured by a high-copy plasmid5Wang J Wang Y Wang ZY et al.Chromosomally located fosA7 in Salmonella isolates from China.Front Microbiol. 2021; 12781306Crossref Scopus (10) Google Scholar or mobile genetic elements (eg, fosA7.5 in Escherichia coli)6Zhang X Ma M Cheng Y et al.Spread and molecular characteristics of Enterobacteriaceae carrying fosA-like genes from farms in China.Microbiol Spectr. 2022; 10e0054522Google Scholar comprising strong promoters, leading to increased gene expression. Therefore, the molecular regulatory mechanism of fosA7 expression in Salmonella should be elucidated, and monitoring this gene should be a standard Salmonella surveillance protocol. We declare no competing interests. This work was supported in part by the National Key Research and Development Program of China (grant number 2022YFC2604200), the National Natural Science Foundation of China (grant number 31902319), the fifth phase of the scientific research 333 project in Jiangsu Province (BRA2020002), and the Priority Academic Programme Development of Jiangsu Higher Education Institution. Download .pdf (.59 MB) Help with pdf files Supplementary appendix